Submissions for variant NM_001289808.2(CRYAB):c.482T>C (p.Ile161Thr)

dbSNP: rs1592506005

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Agnes Ginges Centre for Molecular Cardiology, Centenary Institute	RCV000999592	SCV001156294	uncertain significance	Hypertrophic cardiomyopathy	2018-10-11	criteria provided, single submitter	research	The CRYAB Ile161thr variant has not been reported previously. It is absent from the Genome Aggregation Database (http://gnomad.broadinstitute.org/). We identified this variant in a HCM proband with no family history of disease. The proband also harbours a second variant (TNNT2 Arg278Cys). Computational tools SIFT, MutationTaster, and PolyPhen-2 predict this variant to have a deleterious effect. In summary, based on rarity in the general popualtion and our limited familial data we classify CRYAB Ile161Thr as a variant of "uncertain significance".
Illumina Laboratory Services, Illumina	RCV001103196	SCV001259921	uncertain significance	Myofibrillar myopathy 2	2018-01-12	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 Laboratory Services, Illumina	RCV001103197	SCV001259922	uncertain significance	Fatal infantile hypertonic myofibrillar myopathy	2018-01-12	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 Laboratory Services, Illumina	RCV001105110	SCV001262031	uncertain significance	Cataract 16 multiple types	2018-01-12	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.
Revvity Omics, Revvity	RCV003141922	SCV003828656	uncertain significance	not provided	2019-03-01	criteria provided, single submitter	clinical testing