ClinVar Miner

Submissions for variant NM_000363.5(TNNI3):c.273G>A (p.Ala91=) (rs75491697)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000036281 SCV000059933 benign not specified 2012-04-04 criteria provided, single submitter clinical testing Ala91Ala in Exon 05 of TNNI3: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence and has been identified in 0.5% (14/2998) of Afric an American chromosomes from a broad population by the NHLBI Exome Sequencing Pr oject (http://evs.gs.washington.edu/EVS; dbSNP rs75491697).
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000036281 SCV000230915 benign not specified 2015-04-09 criteria provided, single submitter clinical testing
Invitae RCV000233339 SCV000284654 benign Hypertrophic cardiomyopathy 2020-12-06 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000036281 SCV000920309 benign not specified 2017-09-05 criteria provided, single submitter clinical testing Variant summary: The TNNI3 c.273G>A (p.Ala91Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. MutationTaster predicts a damaging outcome for this variant. 3/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE sites at the locus. However, these predictions have yet to be confirmed by functional studies. This variant was found in 48/113142 control chromosomes from all ethnicities, but was predominantly observed in the African subpopulation at a frequency of 0.005606 (46/8206). This frequency is about 45 times the estimated maximal expected allele frequency of a pathogenic TNNI3 variant (0.000125), strongly suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, the variant was found to co-occur with a pathogenic DSP mutation (c.1dupA) in an internal LCA sample. Additionally, multiple clinical diagnostic laboratories/reputable databases have classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Illumina Clinical Services Laboratory,Illumina RCV001133536 SCV001293240 likely benign Familial restrictive cardiomyopathy 1 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV001133537 SCV001293241 likely benign Familial hypertrophic cardiomyopathy 7 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV001133538 SCV001293242 uncertain significance Dilated cardiomyopathy 2A 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Clinical Services Laboratory,Illumina RCV001133539 SCV001293243 likely benign Familial Hypertrophic Cardiomyopathy with Wolff-Parkinson-White Syndrome 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Color Health, Inc RCV001188353 SCV001355399 benign Cardiomyopathy 2018-10-08 criteria provided, single submitter clinical testing

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