Submissions for variant NM_003126.4(SPTA1):c.3357G>C (p.Lys1119Asn)

gnomAD frequency: 0.00098  dbSNP: rs200230894

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000443048	SCV000536520	uncertain significance	not provided	2017-01-20	criteria provided, single submitter	clinical testing	The K1119N variant in the SPTA1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The K1119N variant was not observed at any significant frequency in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The K1119N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret K1119N as a variant of uncertain significance.
Illumina Laboratory Services, Illumina	RCV001099386	SCV001255838	uncertain significance	Elliptocytosis 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	RCV001099387	SCV001255839	uncertain significance	Pyropoikilocytosis, hereditary	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	RCV001101374	SCV001257976	uncertain significance	Hereditary spherocytosis type 3	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.
Centogene AG - the Rare Disease Company	RCV001101374	SCV002028319	uncertain significance	Hereditary spherocytosis type 3	2016-03-04	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000443048	SCV002505979	uncertain significance	not provided	2022-01-26	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000443048	SCV002541196	uncertain significance	not provided	2022-10-25	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000443048	SCV003822647	uncertain significance	not provided	2023-12-04	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000443048	SCV004327631	benign	not provided	2023-07-08	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004737490	SCV005350337	uncertain significance	SPTA1-related disorder	2024-08-07	no assertion criteria provided	clinical testing	The SPTA1 c.3357G>C variant is predicted to result in the amino acid substitution p.Lys1119Asn. To our knowledge, this variant has not been reported in association with SPTA1-related disorders. This variant is reported in 0.11% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-158622275-C-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.